Bones are made up of osteoid (hard), cartilaginous (tough and flexible), and fibrous (threadlike) tissues, as well as elements of bone marrow. Bone cancer can start in any bone in the body and in any type of bone tissues. If discovered early, bone cancer could be treated by surgery to remove the tumor and the cancerous cells, which would be ideal especially if the tumor and cancerous cells have not spread and can be removed cleanly. More often the treatment needs a combination of surgery with other treatments, such as stem cell transplantation, chemotherapy, radiation therapy, etc. A targeted chemotherapy for the treatment of bone cancers, in principle, requires that the chemotherapy agent, after systemic administration, accumulate in the cancerous bone tissues. This requirement, in addition to the large variety of bone cancers, renders development of bone cancer therapies a challenging task.
Hematologic (or blood) cancer is a close relative to bone cancer since it begins in blood-forming tissue, such as the bone marrow, or in the cells of the immune system. Examples of hematologic cancer are leukemia, lymphoma, and multiple myeloma. In particular, multiple myeloma, a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment, monoclonal protein in the blood or urine, and associated organ dysfunction, accounts for approximately 1% of neoplastic diseases and 13% of hematologic cancers. (Palumbo, A. and Anderson, K.; “Multiple Myeloma,” New. Engl. J. Med., 2011, 364(11): 1046-1060). Although treatments have been developed for multiple myeloma, including alkylating agents, glucocorticoids, immunomodulatory drugs (IMiDs), and proteasome inhibitors, see Chesi, M., et al., Blood, 2012, 120(2), 376-385, multiple myeloma is still considered a fatal B cell malignancy. US 2013/0281377A1.
The platinum-based antineoplastic agents, such as cisplatin, carboplatin, and oxaliplatin, though without an alkyl group, are sometimes described as “alkylating-like” due to their similar effects to those of alkylating antineoplastic agents. Cruet-Hennequart, S., et al. DNA Repair (Amst.), 2008, 7 (4): 582-596. They have been used for treating a variety of cancers, such as ovarian cancer, testicular cancer, small-cell lung cancer, and colorectal cancer.
A new class of platinum-based antitumor agents disclosed in U.S. Pat. Nos. 7,700,649 and 8,034,964, both to R. Bose, namely “phosphaplatin” complexes (because they contain a pyrophosphate group), function as anti-cancer agents without reliance on covalently binding DNA. As a result, they have been found to be efficacious in the treatment of various cisplatin and carboplatin-resistant cancers. These phosphaplatin compounds harbor a pyrophosphate moiety within their composition, which we posit may render these anti-cancer agents selective to targeting cancers that originate in, reside in, or metastasize to the bone.
Examples of such diseases include prostate or other solid tumor cancers that have a propensity to metastasize to bone, and multiple myeloma or other hematological malignancies that originate in bone.